UNSTABLE EXPANSION OF CAG REPEAT IN HEREDITARY DENTATORUBRAL-PALLIDOLUYSIAN ATROPHY (DRPLA)

Hereditary dentatorubral-pallidoluysian atrophy (DRPLA) is an autosoma l dominant neurologic disorder characterized by variable combinations of myoclonus, epilepsy, cerebellar ataxia, choreoathetosis and dementi a. By specifically searching published brain cDNA sequences for the pr esence of CAG repeats we identified unstable expansion of a CAG in a g ene on chromosome 12 in all the 22 DRPLA patients examined. A good cor relation between the size of the CAG repeat expansion and the ages of disease onset is found in this group. Patients with earlier onset tend ed to have a phenotype of progressive myoclonus epilepsy and larger ex pansions. We propose that the wide variety of clinical manifestations of DRPLA can now be explained by the variable unstable expansion of th e CAG repeat.